Detection of IDH1 mutations in a series of 91 oligodendrogliomas: Comparison of immunohistochemistry, DNA sequencing, and allele-specific PCR.

Loussouarn, Delphine; Loupp, Anne-Gaëlle Le; Frenel, Jean Sébastien; Leclair, F.; Deimling, A. Von; Aumont, Maud; Martin, Stéphane; Campone, M.; Denis, M. G.

doi:10.1200/jco.2011.29.15_suppl.2020

Cited by 4 publications

(5 citation statements)

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“…While the frequency of IDH1 mutation that we found in secondary GBMs by immunohistochemistry is lower than that found in most studies, there is a broad range of frequencies reported (50–84.2%) . Most studies have shown that immunohistochemistry for mutant IDH1 protein is comparable in sensitivity to sequencing or PCR in detecting the IDH1 mutation . Similar to our study, Wang et al found that 31% of GBM‐Os contained the IDH1 mutation, compared with less than 5% of conventional GBMs.…”

Section: Discussionsupporting

confidence: 79%

Glioblastoma with Oligodendroglioma Component (GBM‐O): Molecular Genetic and Clinical Characteristics

et al. 2013

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Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM-O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM-Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation-specific polymerase chain reaction (PCR). GBM-Os accounted for 11.9% of all GBMs. GBM-Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM-Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM-O appeared to be associated with a younger age at presentation. Among patients with GBM-O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM-O represents a subset of GBMs with distinctive morphologic, clinical and molecular characteristics.

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Section: Discussionsupporting

confidence: 79%

Glioblastoma with Oligodendroglioma Component (GBM‐O): Molecular Genetic and Clinical Characteristics

et al. 2013

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“…Preusser et al, 2011 [34] compared anti-IDH1-R132H IHC and IDH1 gene sequencing and found concordant results in (98.9%) 94/95 cases. Similarly, Loussouarn et al, 2012 [35] compared results of IHC, DNA sequencing and allele-specific PCR for status of IDH1 mutations in gliomas (oligodendrogliomas) and found IHC to be 100% sensitive and 100% specific for R132H mutation in IDH1.…”

Section: Discussionmentioning

confidence: 99%

Significance and Impact of Changing WHO Classification Systems on Glial Tumors with Special Reference to IDH1 Mutation in Resource-Limited Setups

Singh,

Misra,

Varma

2023

Asian Pac J Cancer Biol

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Objectives: To reclassify glial neoplasms according to the 2021 WHO CNS tumor classification and to study the expression pattern of Isocitrate dehydrogenase 1 (IDH1) mutation by immunohistochemistry(IHC) and to categorize these tumors on the basis of IDH1 mutation. Methods: This retrospective study included patients who were diagnosed as glial tumors on histology (n=60). A detailed clinical history and radiological findings were obtained. Patients above 18 years were taken as adults while age upto 18 years were included in pediatric group. IHC for IDH1 mutation was done using Anti-IDH1 (R132H) antibody. Results: Among all glial tumors, 51.7% (31/60) were assigned IDH1 mutant status and the remaining i.e. 48.3% (29/60) were assigned IDH1 wildtype status. While classifying diffuse gliomas according to age, site and morphology, it was observed that the relative proportion of IDH1 mutant and IDH1 wildtype categories in the adult age group was 56.8% (25/44 cases) and 43.2% (19/44 cases) respectively while in the pediatric age group it was 45.5% (5/11 cases) and 54.5% (6/11 cases) respectively. Among the other glial and glioneuronal tumors majority were IDH1 wildtype (80.0%). Most of the WHO grade 1 tumors were IDH1 wildtype (71.4%, 5/7) whereas Grade 2 and 3 tumors were IDH1 mutant (83.3%, 15/18 and 100.0%, 5/5 respectively). On the other hand in Grade 4 tumors there was a higher proportion of neoplasms exhibiting IDH1 wildtype status (70.0%, 21/30). Conclusion: Identification of IDH status as mutant and wildtype is crucial in glial tumors (especially glioblastoma) because both these groups are clinically, genetically, biologically and prognostically different. IHC provides a standard alternative for molecular studies with high sensitivity and specificity with quick, economical and standard results especially useful in resource-poor countries. Reclassification according to the latest WHO classification appears to confer a overall better prognosis than the previous classifications and this study can also provide a base for future larger research avenues and treatment based on IDH1 mutation.

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“…Primers were used as previously published IDH1wt-F(5'-GGTAAAACCTATCATCATAGGTCG-3'), IDH1mut-F (5'-GGGTAAAACCTATCATCATAGGTCA-3'), and IDH1-R (5'-CACATACAAGTTGGAAATTTCTGG-3'). 22 Amplification was performed on a Rotor Gene Q cycler (Quiagen) using the following conditions (2-step cycling program): initial denaturation for 3 minutes at 95 C followed by 45 cycles of 95 C for 5 seconds and 60 C for 10 seconds. For each run, a melting curve analysis was performed to confirm specificity of the amplification.…”

Section: Real-time Pcrmentioning

confidence: 99%

“…Therefore, IDH1mut IHC and allele-specific PCR were recently introduced as highly sensitive and specific alternative techniques. 22 In addition, quantitative PCR (qPCR) and IHC render a quantitative analysis of IDH1mut possible which was not feasible beforehand. In regard to the potential role of downstream products of mutated IDH1 in gliomagenesis and glioma progression, in this study, we aimed at (1) establishing qPCR as a tool in analysis of IDH1mut status and (2) analyzing the correlation between level of IDH1mut expression and course of the disease.…”

Section: Introductionmentioning

confidence: 99%

Qualitative and Quantitative Analysis of IDH1 Mutation in Progressive Gliomas by Allele-Specific qPCR and Western Blot Analysis

Perrech

Dreher

Röhn

et al. 2019

Technol Cancer Res Treat

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To date, diagnosis of IDH1 mutation is based on DNA sequencing and immunohistochemistry, methods limited in terms of sensitivity and ease of use. Recently, the diagnosis of IDH1 mutation by real-time polymerase chain reaction was introduced as an alternative method. In this study, real-time polymerase chain reaction was validated as a tool for detection of IDH1 mutation, and expression levels were analyzed for correlation with course of the disease. A total of 113 tumor samples were obtained intraoperatively from 84 patients with glioma having a diagnosis of diffuse glioma (World Health Organization II), anaplastic glioma (World Health Organization III), secondary glioblastoma ± chemotherapy, primary glioblastoma ± chemotherapy (World Health Organization IV). Tumor samples were snap frozen and processed for sectioning and RNA and protein isolation. Presence of IDH1 mutation was determined by DNA sequencing. Hereafter, quantitative expression of IDH1 messenger RNA was assessed using real-time polymerase chain reaction with specific primers for IDH1 mutation and –wt; protein expression was verified by Western Blot analysis and immunohistochemistry. Additionally, 19 samples of low-grade glioma and their consecutive high-grade glioma were analyzed at different time points of the disease. IDH1 mutation was identified in 63% of samples by DNA sequencing. In correlation with the real-time polymerase chain reaction results, a cutoff value was determined. Above this threshold, sensitivity and specificity of real-time polymerase chain reaction in detecting IDH1 mutation were 98% and 94%, respectively. Quantitative analysis revealed that IDH1 mutation expression is upregulated in secondary glioblastoma (mean ± standard error of mean: 3.52 ± 0.55) compared to lower grade glioma (II = 1.54 ± 0.22; III = 1.67 ± 0.23). In contrast, IDH1 wt expression is upregulated in all glioma grades (concentration >0.1) compared to control brain tissue (0.007 ± 0.0016). Western Blot analysis showed a high concordance to both sequencing and real-time polymerase chain reaction results in qualitative analysis of IDH1 mutation status (specificity 100% and sensitivity 100%). Moreover, semiquantitative protein expression analysis also showed higher expression levels of mutated IDH1 in secondary glioblastoma. In our study, real-time polymerase chain reaction and Western Blot analysis were found to be highly efficient methods in detecting IDH1 mutation in glioma samples. As cost-effective and time-saving methods, real-time polymerase chain reaction and Western Blot analysis may therefore play an important role in IDH1 mutation analysis in the future. IDH1 mutation expression level was found to correlate with the course of disease to a certain extent. Yet, clinical factors as recurrent disease or prior radiochemotherapy did not alter IDH1 mutation expression level.

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Detection of IDH1 mutations in a series of 91 oligodendrogliomas: Comparison of immunohistochemistry, DNA sequencing, and allele-specific PCR.

Cited by 4 publications

References 0 publications

Glioblastoma with Oligodendroglioma Component (GBM‐O): Molecular Genetic and Clinical Characteristics

Glioblastoma with Oligodendroglioma Component (GBM‐O): Molecular Genetic and Clinical Characteristics

Significance and Impact of Changing WHO Classification Systems on Glial Tumors with Special Reference to IDH1 Mutation in Resource-Limited Setups

Qualitative and Quantitative Analysis of IDH1 Mutation in Progressive Gliomas by Allele-Specific qPCR and Western Blot Analysis

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